Targeted gene disruptions in mice (knockouts) have helped define the functions of several nuclear genes encoding products that function within mitochondria (as described in the text) including: Tfam (orange spheres), binds the mtDNA at multiple sites and functions in both mtDNA maintenance and transcription initiation; Mterf3, functions as a negative regulator of mtDNA transcription; Tfb1m (red ellipse) and Mterf4 (green ellipse), participate in mitochondrial ribosome assembly. Tfb1m is a dimethyltransferase that catalyzes the adenine dimethylation of the small ribosomal RNA required for ribosome assembly and translation. Similarly, a complex containing Mterf4 and the rRNA methyltransferase, NSUN4 (blue ellipse), participates in the assembly of the large ribosomal subunit.